Influence of methylphenidate on brain development – an update of recent animal experiments

Methylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. In spite of its widespread application throughout one of the most plastic and sensitive phases of brain development, very little is known to date about its long-term effects on brain structure and function. Hence, this short review updates the influence of MPH on brain development, since recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment.     

HLA-D typing in Austria. A panel study using 26 newly defined homozygous typing cells

A panel of 120 HLA-A, -B, -C and -DR typed Austrians has been typed for HLA-D by the use of 26 Homozygous Typing Cells (HTC). The new Austrian HTC, partly defined by the 9th International Histocompatibility Workshop (9WS), partly by a checkerboard experiment with internationally well defined reference HTC, type for HLA-Dw1 to -Dw7 and an obviously new, so far unknown HLA-DR2 related HLA-D determinant. Associations of HLA-DR and HLA-D antigens in Austria and their frequencies are determined. Antigen frequencies in Austria are compared to frequencies in other Caucasoid populations.     

α1B- but not α1A-adrenoceptors mediate inositol phosphate generation

Summary We used novel highly subtype-selective antagonists to study whether _1A- and/or _1B-adrenoceptors mediate the stimulation of inositol phosphate generation by noradrenaline in rat cerebral cortex. Phentolamine (10 M) and prazosin (100 nM) completely abolished the stimulated inositol phosphate generation. The _1A-selective antagonists 5-methyl-urapidil (100 nM) and (+)– and (–)-niguldipine (10 nM) caused only weak inhibition or none at all although these concentrations occupied _1A-adrenoceptors almost completely. In contrast, pretreatment with the irreversible _1B-selective chloroethylclonidine reduced the noradrenaline-stimulated inositol phosphate generation by 76 ± 8%. These data demonstrate that _1B-adrenoceptors couple to inositol phosphate generation; the signal transduction system of _1A-adrenoceptors remains unclear. Send offprint requests to G. Gross at the above address     

A pilot study of mammographic density patterns among Japanese women.

Mammographic density patterns, which refer to the distribution of fat, connective, and epithelial tissue in the healthy female breast, have been shown to be related to breast cancer risk. We used a quantitative method to assess mammographic densities in 41 mammograms from women in Japan without a diagnosis of breast cancer. Information about reproductive behavior and family history for breast cancer was available from a questionnaire. The statistical analysis applied Spearman correlation coefficients and multiple linear regression. The breast size as measured on the cranio-caudal view of the mammogram was approximately 12% larger, the size of the dense areas was 20% smaller, and the mean percent mammographic densities were 30% greater among premenopausal than among postmenopausal women. We found a strong relation between age at menarche and mammographic densities in premenopausal women and significant associations for age, family history of breast cancer, and age at menopause with mammographic densities in postmenopausal women. These preliminary data will be used to plan a future study that will compare mammographic density patterns and the relative importance of dietary, reproductive, and anthropometric factors between women in Japan and in the United States.     

Association of genetic polymorphisms with serum estrogens measured multiple times during a 2-year period in premenopausal women.

There is evidence that circulating estrogens are associated with breast cancer risk. In this study of premenopausal women, we explored the association of polymorphisms in genes in the estrogen synthesis and metabolism pathways with serum and urinary levels of estrone (E1) and estradiol (E2) and with the urinary ratio of 2-hydroxyestrone (2-OHE1)/16alpha-hydroxyestrone (16alpha-OHE1). This analysis included 220 women, who were participants in a 2-year randomized soy intervention. Blood specimens were collected in the luteal phase of the menstrual cycle an average of 4.4 times over 2 years. Overnight urinary specimens were collected on the same cycle day, only at baseline. Levels of E1, E2, 2-OHE1, and 16alpha-OHE1 were measured by enzyme immunoassays. The DNA samples were analyzed by PCR/RFLP for the COMT Val158Met, CYP1A1*2A, CYP1A1*2B, CYP1A2*1F, CYP1B1 Val432Leu, and CYP17 T27C polymorphisms. We applied mixed models to investigate the relations between genotypes and repeated serum hormone measurements and generalized linear models to assess associations between genotypes and urinary estrogen metabolites. The CYP1A2 C allele was significantly associated with lower serum E2 levels; in CC genotype carriers, serum E2 levels were 26.3% lower than in homo- and heterozygous common allele carriers combined (P = 0.01). CYP1A2*1F also affected the urinary 2-OHE1/16alpha-OHE1 ratio; carriers of the variant C allele had a markedly lower ratio than individuals with the AA genotype (1.37 versus 1.76; P = 0.002). These data suggest that CYP1A2*1F is associated with lower circulating levels of E2, and that it may be a susceptibility locus for breast cancer.     

Repair of erosions in rheumatoid arthritis does occur. Results from 2 studies by the OMERACT Subcommittee on Healing of Erosions

The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.     

Prediagnostic circulating carotenoid levels and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort

This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for β-carotene. Other carotenoids, including α-carotene, β-carotene, lutein, β-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL.